1. Field
The disclosure of the present patent application relates generally to piperazine/morpholine linked dihydropyrimidinone derivatives, and methods for preparing these derivatives. In particular, the application focuses on 4-(substituted phenyl)-5-[4-(piperazin/morpholin-1-yl) benzoyl]-3,4-dihydropyrimidin-2(1H)-one derivatives and methods for their preparation.
2. Description of the Related Art
Piperazine consists of six membered heterocyclic rings containing two nitrogen atoms at two opposite positions. Piperazine moiety containing polar nitrogen atoms confers bioactivity to the molecule and increases favorable interactions with macromolecules. Piperazine has the ability to cross the blood brain barrier (BBB) due to its small size and lipophilic nature which promote its activity upon central nervous system (CNS) diseases which include anxiety disorders, Alzheimer's disease, psychosis and depression. Many potent marketed drugs like flunarizine, cinnarizine, lomerizine, fluphenazine, ciprofloxacin, Merck HIV protease, and crixivan, have a piperazine moiety. Piperazine derivatives have been found to be potent agents in the treatment of various ailments, such as CNS agents, anticancer, cardio-protective agents, antiviral, anti-tuberculosis, anti-inflammatory, anti-diabetic, and antihistamine profiles, as well as agents for relieving pain and for use in imaging applications.
Morpholine is an organic moiety containing nitrogen and oxygen in a heterocyclic six membered ring and is considered an important building block in the field of medicinal chemistry. The Linezolid antibiotic having a morpholine moiety is commercially available as an antimicrobial agent. A selective inhibitor of epidermal growth factor Timolol (non-selective beta-adrenergic receptor antagonist indicated for treating glaucoma) Moclobemide, Emorfazone (anti-inflammatory drug and analgesic), Phenadoxone (Heptalgin, opioid analgesic), anti-depressants Reboxetine and Gefitinib, appetite suppressants Phenmetrazine (Preludin, 3-methyl-2-phenylmorpholine) and 2-benzylmorpholine and Canertinib, Fenpropimorph (fungicide), and antibacterial drugs Finafloxacin, Levofloxacin. Morpholine derivatives are very essential in the drug discovery process. The morpholine scaffold is important due to its variety of pharmacological activities, including analgesic, anti-inflammatory, anticancer, antidepressant, HIV-protease inhibitors, appetite suppressant, local anaesthetic, antiplatelet, selective inhibitor of protein kinase C, antitumor, neuroprotective, antifungal, anti-tuberculosis, anti-parasitic, anti-malarial, hypolipidemic and hypocholesterolemic activities.
Pyrimidines have played an important role in medicinal chemistry. Pyrimidines are important scaffolds in the field of medicinal chemistry because of their potential biological activities, including use as anti-tumor, anti-virus and anti-bacterial agents. Some pyrimidines have been used as potential anti-hypertensive agents. 4-Aryl-1,4-dihydropyridines, like Nifedipine, were first introduced as antihypertensive agents used in medicine in 1975. Dihydropyridines are the most potent calcium channel modulators available for the treatment of various cardiovascular diseases.
Substituted dihydropyrimidinone compounds have been shown to possess interesting biological properties. Some of the analogs of dihydropyrimidine compounds are antitumor agents. Dihydropyrimidinones have emerged as the integral back bone of calcium channel blockers, or antihypertensive agents. Some of these compounds have exhibited a broad range of other biological activities such as antiviral, antitumor, antibacterial and anti-inflammatory.
Dihydropyrimidinone compounds were first synthesized by Pietro Beginelli. The compounds were known as Biginelli compounds. The compounds were produced by reacting aldehydes with urea and a beta-keto ester, producing a tetrahydropyrimidinone.
Since Biginelli's time, a number of procedures have been described for synthesizing dihydropyrimidinone compounds and their derivatives. However, in view of the established medical and pharmaceutical value of this family of compounds, there is still a need for new dihydropyrimidinone compounds and synthesis procedures.
Thus, dihydropyrimidinone derivatives solving the aforementioned problems is desired.